大肠腺癌组织中的Glut1和HIF-1α蛋白表达及其与癌细胞增殖的相关性

Correlations of Expressions of Glut1 and HIF-1α to Cellular Proliferation of Colorectal Adenocarcinoma

背景与目的:恶性肿瘤细胞表现出微环境缺氧和糖代谢增加,缺氧时葡萄糖转运蛋白1(glucosetransporter-1,Glut1)和缺氧诱导因子-1α(hypoxia-induciblefactor1alpha,HIF鄄1α)促进糖代谢增加。两者在大肠腺癌中表达的关联性分析及与增殖活性的关系尚未见报道,本研究旨在探讨两者在大肠腺癌组织中的表达及与细胞增殖活性的关系。方法:采用免疫组织化学方法检测Glut1、HIF-1α、增殖细胞核抗原(proliferatingcellnuclearantigen,PCNA)在60例大肠腺癌组织及20例正常大肠组织的表达水平,并比较它们之间相关性。结果:Glut1、HIF-1α在大肠腺癌组织中的表达阳性率分别为58.3%和73.3%,在正常大肠组织中无表达,与正常大肠组织表达比较差异有显著性(均P<0.01),PCNA在大肠腺癌组织中的表达(65.25±16.35)显著高于正常组织中的表达(15.20±3.47)(P<0.01)。Glut1、HIF-1α蛋白表达与PCNA呈正相关(r1=0.409,P<0.01和r2=0.323,P<0.05),与淋巴结转移、Dukes分期相关。结论:Glut1和HIF-1α蛋白的过表达共同参与了大肠腺癌的发生、发展,与大肠腺癌细胞增殖活性密切相关。

BACKGROUND & OBJECTIVE: Malignant cells exhibit increased glucose metabolism and microenvironment hypoxia. Glucose transporter-1 (Glut1) and hypoxia-inducible factor 1 alpha (HIF-1α) enhance glucose metabolism under hypoxia. This study was to investigate the expressions of Glut1 and HIF-1α in colorectal adenocarcinoma, and explore their correlations to cell proliferation. METHODS: Immunohistochemistry was used to detect expressions of Glut1, HIF-1α, and proliferating cell nuclear antigen (PCNA) in 60 specimens of colorectal adenocarcinoma and 20 specimens of normal colorectal tissues. Their interrelations were analyzed. RESULTS: Positive rates of Glut1 and HIF-1α were significantly higher in colorectal adenocarcinoma tissues than in normal colorectal tissues (58.3% vs. 0, P < 0.01; 73.3% vs. 0, P < 0.01). PCNA level was significantly higher in colorectal adenocarcinoma tissues than in normal colorectal tissues (65.25±16.35 vs. 15.20±3.47, P < 0.01). Glut1 and HIF-1α levels were positively correlated with PCNA level (r1=0.409, P < 0.01; r2=0.323, P < 0.05), and were associated with Dukes?蒺 stage and lymph node metastasis. CONCLUSIONS: The overexpressions of Glut1 and HIF-1α play important roles in carcinogenesis and progression of colorectal adenocarcinoma, and closely correlate with cell proliferation of colorectal adenocarcinoma.